Dear readers, the gut microbiota is known for long to have the ability to act on our brain. Nevertheless, a bidirectional gut-brain communication system in which our gut microbiota participates has only been identified and studied as a “microbiota - gut - brain axis” since a dozen years. More recently, studies have suggested that dysbiosis could contribute to the pathophysiology of central nervous system diseases such as anxiety and depressive disorders, autism spectrum disorders, Alzheimer’s disease or Parkinson’s disease, while these last two diseases tend to be spontaneously related to brain damage.

In 2017, American researchers have named “mapranosis” (for Microbiota Associated PRoteopathy And Neuroinflammation) a concept relating the microbiota to Parkinson’s and Alzheimer’s diseases.

Their research has highlighted the involvement of gut bacteria producing amyloid proteins likely to increase the production of α-synuclein in the gut. This protein, in an inadequate conformation, could be transported via the gut-brain axis and promote the formation of aggregates in the brain, leading to neurodegenerative damage.

As part of this scientific stream, Prof. John F. Cryan (APC Microbiome Institute, Cork, Ireland) is particularly interested in the role of the microbiota in neurodevelopment, neuroinflammation and aging processes. In this newsletter, he explains how Parkinson’s and Alzheimer’s diseases could originate from the gut and describes dysbiosis associated with these neurodegenerative diseases, as well as the possible role of the vagus nerve.

For his part, Prof. Emmanuel Mas (Children’s Hospital, Toulouse, France) discusses the role of the microbiota - gut - brain axis in psychiatric diseases. He comments on the results of a recent Chinese study reporting gut dysbiosis in children with attention deficit hyperactivity disorder (ADHD). According to this work, the abundance of Faecalibacterium in the gut microbiota could be negatively correlated with the severity of ADHD.

As evidenced by these contributions, the research and application perspectives appear promising, although the mechanisms by which the microbiota influences - or is correlated with - these diseases remain to be further explored.

Enjoy your reading!

THE GUT MICROBIOME AND NEURODEGENERATION

by By Prof. John F. Cryan Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland

The past decade has seen an explosion of research in the role of the gut microbiota in modulating brain health and disease. Although most research has focused on stress-related disorders, such as anxiety, depression and irritable bowel syndrome, a growing body of research, albeit largely preclinical, also implicates the microbiota as a disease moderator in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In tandem, research has shown that the microbiome plays a critical role in key brain processes involved in neurodevelopment, neuroinflammation, and aging. Currently, research is heavily focused on a better understanding of the precise mechanisms of how the gut talks to the brain and how it may lead to increased susceptibly to brain disorders.

Clostridium difficile has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here the authors show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor* that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. The authors propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.

Although increasing evidence suggests a role for the gut microbiota in neurodevelopment, the actual structure and composition of microbiota in children with attention-deficit/hyperactivity disorder (ADHD) remain unclear. Thus, the present study aimed to define the characteristics of gut microbiota in treatment-naive children with ADHD and to assess their relationship with the severity of ADHD symptoms. High-throughput pyrosequencing was used to investigate the microbiota composition in fecal matter from 51 children with ADHD and 32 healthy controls (HC). An operational taxonomical unit (OTU)-level analysis revealed a significant decrease in the fractional representation of Faecalibacterium in children with ADHD compared to HC. In individuals with ADHD, the abundance of Faecalibacterium was negatively associated with parental reports of ADHD symptoms. However, there was no significant difference in alpha diversity between the ADHD and control groups. This present findings support the involvement of microbiota alteration in psychiatric diseases and Faecalibacterium may represent a potential novel marker of gut microbiota in ADHD. Future studies are needed to validate these findings and to elucidate the temporal and causal relationships between these variables.

MICROBIOTA AND NON-ANTIBIOTIC DRUGS INTERACTIONS: FRIENDS OR FOES?

Previous studies showed that metformin, proton pump inhibitors, NSAIDs, and atypical antipsychotics have an effect on the intestinal microbiota composition. However, these studies presented general results for drug classes instead of specific drugs.

MICROBIOTA AND CYSTIC FIBROSIS

Cystic fibrosis (CF) is a progressive, genetic disease that causes persistent lower respiratory infections and is related to different systemic symptoms and signs. More than 70,000 people live with CF worldwide. The types and severity of symptoms can differ widely from person to person and are mainly related to the age of the patient as well as age at diagnosis. Children and adolescents with CF have a wide range of symptoms and signs including gastrointestinal manifestations.

Report from the conference

10/05

ESPGHAN

Geneva - Switzerland

Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria are the most abundant phyla in H. pylori positive and H.pylori-negative patients and this gastric microbiota may play a role in the H. pylori-associated carcinogenicity. Alarcón characterized gastric microbiota in children with and without H. pylori; when detected, H. pylori dominated the microbial community, but when absent, there was a higher bacterial richness and diversity.

01/09

FNM

Amsterdam - The Netherlands

Microbiota dysbiosis and its relation to irritable bowel syndrome (IBS) was discussed during various sessions of the conference. In particular, Prof. Magnus Simrén and Prof. Uday Ghoshal highlighted some features related to microbiota composition of IBS patients.